The study involves determining the control of fatty acid metabolism in isolated rat hearts perfused under conditions which allow the level of cardiac work to be varied over a wide range, the availability and type of substrates to be altered at will and provide for ease of determining metabolic rates. Since the heart derives its energy primarily from oxidation of fatty acids under normal conditions, and almost entirely from fatty acids and ketone bodies in diabetes and fasting, any increase in energy expenditure (greater myocardial workloads, for example) probably is accounted for by oxidation of fatty acids. The mechanism of increased utilization of fatty acid with increased ventricular pressure development is poorly understood, but maintenance of this potential may be essential for continued performance of the heart under high workloads. The work proposed in this application relates to understanding the overall control of fatty acid metabolism under control conditions. In addtition, information on the factor regulating FFA utilization is of general interest in a variety of physiological and pathological states. The isolated perfused rat heart appears to be a good experimental system with which to define these factors since rates of fat oxidation can be varied with ease.